Successful Management of Refractory Kimura Disease with CVP Chemotherapy: A Case Report.

BACKGROUND Kimura disease is a rare, chronic inflammatory disorder typically presenting as a painless mass in the head or neck and associated with elevated serum immunoglobulin E and blood and tissue eosinophilia. Generally benign, its management is not well-defined, but corticosteroids are a common initial treatment. We detail a case of refractory Kimura disease successfully managed with CVP (Cyclophosphamide, Vincristine, Prednisone) chemotherapy and no recurrence during 6 rounds of treatment. CASE REPORT A 64-year-old woman, previously diagnosed with Kimura disease, returned to the hospital with upper eyelid ptosis. Upon examination, a solid mass was palpable in her left upper eyelid. Peripheral blood tests confirmed elevated IgE levels at 356.0 IU/ml. An excisional biopsy showed infiltration of lymphocytes and eosinophils, consistent with Kimura disease. Despite undergoing corticosteroid treatment, surgical debulking, radiation, and immunosuppressant therapy, her condition worsened. Concerns were raised due to imaging features suggestive of lymphoma, although no malignancy was evident in subsequent biopsies. It was decided to manage the disease using CVP chemotherapy, leading to significant symptom improvement. There have been no recurrences during the 12-month follow-up period. CONCLUSIONS Kimura disease is typically benign and responsive to treatment, but it often recurs and can progress. When symptoms are not controlled with conventional treatments, including corticosteroids, immunosuppressants, radiation, and surgical debulking, chemotherapy may be a reasonable option even when no definite signs of malignancy is identified. Further research is needed to explore the utility of CHOP and CVP in managing uncontrolled Kimura disease.

Clinical Results According to Inferior Oblique Manipulation in Patients with Inferomedial Blowout Fracture Involving the Orbital Strut.

Background: Detachment of the inferior oblique muscle may be necessary under certain circumstances to repair a large inferomedial orbital fracture involving the orbital strut. This study aimed to evaluate the outcomes of patients who underwent surgeries with and without inferior oblique muscle reattachment after its detachment to repair the orbital wall fractures. Methods: Forty patients who underwent repair of combined floor and medial orbital wall fracture involving the orbital strut at a single tertiary institution between January 2014 and December 2020 were reviewed. Groups 1 and 2 comprised 20 patients each, who underwent surgery with inferior oblique muscle detachment without and with reattachment, respectively, and were followed up for at least 6 months postoperatively. Enophthalmos, Goldmann diplopia test, alignment test, ocular motility test, and orbital inferomedial angle ratio were the outcome measures. Results: Statistically significant improvement was observed in ocular motility, diplopia, and enophthalmos postoperatively at the 1- and 6-month follow-up (p < 0.01). The mean postoperative inferomedial angle ratio (102.28 ± 10.62%) was improved significantly compared with the preoperative inferomedial angle ratio (115.61 ± 4.38%) (p = 0.004) in all patients. After surgery, inferior oblique muscle underaction was observed in seven and six patients in groups 1 and 2, respectively, which was associated with preoperative extraocular movement limitation and strabismus. Two patients showed diplopia in both groups at the last follow-up; they had inferior oblique muscle underaction but no enophthalmos. Conclusion: Orbital fracture repair with or without inferior oblique muscle reattachment was clinically effective and safe; however, patients with preoperative strabismus and extraocular motility limitation should be informed of the increased risk of postoperative complications.

Ligamentum flavum hypertrophy significantly contributes to the severity of neurogenic intermittent claudication in patients with lumbar spinal canal stenosis.

Ligamentum flavum hypertrophy (LFH) is a known contributor to lumbar spinal canal stenosis (LSCS). However, the clinical significance and quantitative role of LFH compared to other components, such as disc bulging and facet hypertrophy, have not yet been examined. We investigated the correlation between the quantitative radiological factors, clinical symptoms, and outcomes in patients with LSCS. In total, 163 patients diagnosed with single-level (L4-L5) stenosis were included. The patients were divided into 2 groups according to claudication severity: >100 m for mild (n = 92) and < 100 m for severe (n = 71). The visual analog scale (VAS) was used to quantify back and leg pain, and the Oswestry Disability Index (ODI) and Short form-36 (SF-36) physical component summary (PCS) scores, and Macnab criteria were evaluated as clinical factors 6 months after treatment. We measured the baseline canal cross-sectional area, ligamentum flavum (LF) area, disc herniation area, dural sac area, fat area, and LF thickness using MRI. A comparative analysis was performed to evaluate the association between radiologic and clinical factors. Additionally, further comparative analyses between the types of surgeries were performed. Among various radiologic factors, the baseline LF thickness (odds ratio [OR] 1.73; 95% confidence interval [CI] 1.25-2.41) was the only major contributing factor to the severity of claudication in the multivariate logistic regression analysis. The types of surgery (decompression alone vs fusion) did not significantly differ in terms of their clinical outcomes, including back and leg VAS, ODI, SF-36 PCS, and satisfaction with the MacNab classification. LF thickness is a major factor contributing to claudication severity.

Identification of optimal surgical plan for treatment of extraocular muscle damage in thyroid eye disease patients based on computational biomechanics.

This study replicated the behavior of intraorbital tissue in patients with thyroid eye disease (TED) based on finite element analysis for general orbital decompression risk evaluation in thyroid eye disease patients. The orbit and intraorbital tissues of thyroid eye disease patients who underwent orbital decompression were modeled as finite element models. The stress was examined at specific locations of the removed orbital wall of a thyroid eye disease patient with undergone orbital decompression, and its variation was analyzed as a function of the shape and dimension (to be removed). As a result, in orbital decompression surgery which removes the orbital wall in a rectangular shape, the stress at the orbital wall decreased as the width and depth of the removed orbital wall increased. In addition, in the case of orbital decompression, it can be seen that the chamfered model compared to the non-chamfered model (a form of general orbital decompression) have the stress reduction rate from 11.08% to 97.88%. It is inferred that if orbital decompression surgery considering the chamfered model is performed on an actual thyroid eye disease patient, it is expected that the damage to the extraocular muscle caused by the removed orbital wall will be reduced.

Extraocular Pressure Measurements to Avoid Orbital Compartment Syndrome in Aneurysm Surgery.

BACKGROUND: Orbital compartment syndrome (OCS) is a rare but devastating complication following pterional craniotomy. Although the causes of OCS are unclear, external compression of the orbit by a myocutaneous flap is commonly mentioned as a major factor. We evaluated the ocular influence of external compression using an extraocular pressure monitor. METHODS: We measured extraocular pressure in 86 patients who underwent surgery for cerebral aneurysm via a pterional approach. Clinical information and radiologic parameters, including the area of the medial rectus muscle (MRM) and the craniotomy height from the bottom of the anterior skull base, were collected. As a control group, 117 patients who underwent surgery without pressure monitoring were also evaluated. RESULTS: Extraocular pressure reached a maximum during craniotomy (mean, 22.0 mm Hg; range, 18.4-51.0 mm Hg) and decreased after myocutaneous flap adjustment (mean, 7.9 mm Hg; range, 5.4-17.5 mm Hg). Pressure before myocutaneous flap manipulation differed between patients with anterior communicating artery (Acomm) aneurysms and other patients (mean, 16.5 mm Hg vs. 9.4 mm Hg; P = 0.003). Among Acomm aneurysm cases, the monitored group showed a significantly lower MRM swelling ratio (postoperative MRM area/preoperative MRM area) compared with the control group (1.03 ± 0.10 vs. 1.17 ± 0.15; P = 0.036). CONCLUSIONS: Myocutaneous flaps can produce unnoticed overpressure on the orbit, resulting in OCS-related blindness during aneurysm clipping surgery, especially in cases involving mandatory lower craniotomy. The continuous extraocular compressive pressure monitoring technique is a simple and effective approach to prevent such a serious complication.

Intravitreal implantable magnetic micropump for on-demand VEGFR-targeted drug delivery.

In this paper, we propose an intravitreal implantable magnetic micropump integrated with micro check valve capable of on-demand vascular endothelial growth factor receptor (VEGFR)-targeted drug delivery for the treatment of age-related macular degeneration, diabetic retinopathy and other eye pathologies characterized by ocular neoangiogenesis. Precise on-demand drug release is realized by the deflection of the magnetic membrane assembly according to the external magnetic field, and the membrane assembly consists of a thin elastic polydimethylsiloxane (PDMS) membrane and a cylindrical magnetic nanoparticle-PDMS composite block. Additionally, a micro check valve composed of two PDMS layers was integrated into the micropump to realize a diode-like one-directional drug delivery and prevent undesired drug diffusion. For specifically targeting VEGFR and suppression of VEGF-induced proliferation of microvascular endothelial cells, anti-Flt1 gold nanocomplexes are synthesized. In vitro and in vivo experiments and quantitative analysis are carried out in order to verify our proposed concept: precise drug release control according to the external magnetic field, targeting to microvascular endothelial cells, and efficient and on-demand drug delivery from the proposed micropump to the macular area of rabbit's eye.

Engineering spheroids potentiating cell-cell and cell-ECM interactions by self-assembly of stem cell microlayer.

Numerous methods have been reported for the fabrication of 3D multi-cellular spheroids and their use in stem cell culture. Current methods typically relying on the self-assembly of trypsinized, suspended stem cells, however, show limitations with respect to cell viability, throughput, and accurate recapitulation of the natural microenvironment. In this study, we developed a new system for engineering cell spheroids by self-assembly of micro-scale monolayer of stem cells. We prepared synthetic hydrogels with the surface of chemically formed micropatterns (squares/circles with width/diameter of 200 µm) on which mesenchymal stem cells isolated from human nasal turbinate tissue (hTMSCs) were selectively attached and formed a monolayer. The hydrogel is capable of thermally controlled expansion. As the temperature was decreased from 37 to 4 °C, the cell layer detached rapidly (<10 min) and assembled to form spheroids with consistent size (∼100 µm) and high viability (>90%). Spheroidization was significantly delayed and occurred with reduced efficiency on circle patterns compared to square patterns. Multi-physics mapping supported that delamination of the micro-scale monolayer may be affected by stress concentrated at the corners of the square pattern. In contrast, stress was distributed symmetrically along the boundary of the circle pattern. In addition, treatment of the micro-scale monolayer with a ROCK inhibitor significantly retarded spheroidization, highlighting the importance of contraction mediated by actin stress fibers for the stable generation of spheroidal stem cell structures. Spheroids prepared from the assembly of monolayers showed higher expression, both on the mRNA and protein levels, of ECM proteins (fibronectin and laminin) and stemness markers (Oct4, Sox2, and Nanog) compared to spheroids prepared from low-attachment plates, in which trypsinized single cells are assembled. The hTMSC spheroids also presented enhanced expression levels of markers related to tri-lineage (osteogenic, chondrogenic and adipogenic) differentiation. The changes in microcellular environments and functionalities were double-confirmed by using adipose derived mesenchymal stem cells (ADSCs). This spheroid engineering technique may have versatile applications in regenerative medicine for functionally improved 3D culture and therapeutic cell delivery.

Nanochannel-Confined TAMRA-Polypyrrole Stained DNA Stretching by Varying the Ionic Strength from Micromolar to Millimolar Concentrations.

Large DNA molecules have been utilized as a model system to investigate polymer physics. However, DNA visualization via intercalating dyes has generated equivocal results due to dye-induced structural deformation, particularly unwanted unwinding of the double helix. Thus, the contour length increases and the persistence length changes so unpredictably that there has been a controversy. In this paper, we used TAMRA-polypyrrole to stain single DNA molecules. Since this staining did not change the contour length of B-form DNA, we utilized TAMRA-polypyrrole stained DNA as a tool to measure the persistence length by changing the ionic strength. Then, we investigated DNA stretching in nanochannels by varying the ionic strength from 0.06 mM to 47 mM to evaluate several polymer physics theories proposed by Odijk, de Gennes and recent papers to deal with these regimes.

World Health Organization Grade II Oligodendroglioma Occurring after Successful Treatment for Childhood Acute Lymphoblastic Leukemia.

When treating childhood acute lymphoblastic leukemia (ALL), secondary neoplasms are a significant long term problem. Radiation is generally accepted to be a major cause of the development of secondary neoplasms. Following treatment for ALL, a variety of secondary tumors, including brain tumors, hematologic malignancies, sarcomas, thyroid cancers, and skin cancers have been reported. However, oligodendroglioma as a secondary neoplasm is extremely rare. Herein we present a case of secondary oligodendroglioma occurring 13 years after the end of ALL treatment.

Role of vincristine in the inhibition of angiogenesis in glioblastoma.

OBJECTIVE: Vincristine, a microtubule-destabilizing drug, was found to exhibit anti-angiogenic effects and anti-tumoral activity. However, the precise mechanism by which vincristine inhibits angiogenesis in glioblastomas is not well understood. Our aim was to investigate whether vincristine affects vascular endothelial growth factor (VEGF) expression in glioblastoma cells and determine whether it is mediated by the downregulation of hypoxia-inducible factor-1α (HIF-1α). METHODS: We investigated the expression of HIF-1α in glioblastoma tissues resected from patients and in human glioblastoma cell lines using immunohistochemistry, Western blot analysis, and immunocytochemistry. In addition to an MTT assay assessing the effect of vincristine on cell proliferation and viability, the effects of vincristine on VEGF mRNA expression and HIF-1α protein were examined using real-time RT-PCR and Western blot analysis under 1% O2 (hypoxia). RESULTS: HIF-1α was expressed in the majority of glioblastoma tissues and was detected mainly in the nucleus. Strong immunoreactivity for HIF- 1 α was found often in the hypercellular zones. Under hypoxic conditions, HIF-1α protein levels in the glioblastoma cell lines increased, primarily localizing into the nucleus similar to glioblastoma tissues. Exposure of glioblastoma cells to vincristine resulted in enrichment of the G2-M fraction of the cell cycle, which suggests that vincristine-mediated growth inhibition of glioblastoma is correlated with mitotic inhibition. Using doses lower than those found to reduce the viability and proliferation of cells by 50% (IC50), vincristine decreased both the expression of VEGF mRNA and the level of HIF-1α protein in hypoxic glioblastoma cells. In addition, following exposure to vincristine, the expression of VEGF mRNA was correlated with HIF-1α protein levels. CONCLUSIONS: Our results suggest that the mechanism by which vincristine elicits an anti-angiogenic effect in glioblastomas under hypoxic conditions might be mediated, in part, by HIF-1α inhibition.

Intrathecal transplantation of autologous adipose-derived mesenchymal stem cells for treating spinal cord injury: A human trial.

CONTEXT: Spinal cord injury (SCI) can cause irreversible damage to neural tissues. However, there is currently no effective treatment for SCI. The therapeutic potential of adipose-derived mesenchymal stem cells (ADMSCs) has been emerged. OBJECTIVE: We evaluated the effects and safety of the intrathecal transplantation of autologous ADMSCs in patients with SCI. Participants/Interventions: Fourteen patients with SCI were enrolled (12 for ASIA A, 1 for B, and 1 for D; duration of impairments 3-28 months). Six patients were injured at cervical, 1 at cervico-thoracic, 6 at thoracic, and 1 at lumbar level. Autologous ADMSCs were isolated from lipoaspirates of patients' subcutaneous fat tissue and 9 × 107 ADMSCs per patient were administered intrathecally through lumbar tapping. MRI, hematological parameters, electrophysiology studies, and ASIA motor/sensory scores were assessed before and after transplantation. RESULTS: ASIA motor scores were improved in 5 patients at 8 months follow-up (1-2 grades at some myotomes). Voluntary anal contraction improvement was seen in 2 patients. ASIA sensory score recovery was seen in 10, although degeneration was seen in 1. In somatosensory evoked potential test, one patient showed median nerve improvement. There was no interval change of MRI between baseline and 8 months post-transplantation. Four adverse events were observed in three patients: urinary tract infection, headache, nausea, and vomiting. CONCLUSIONS: Over the 8 months of follow-up, intrathecal transplantation of autologous ADMSCs for SCI was free of serious adverse events, and several patients showed mild improvements in neurological function. Patient selection, dosage, and delivery method of ADMSCs should be investigated further.

A Rare Case of Malignant Lymphoma Occurred at Spinal Epidural Space: A Case Report.

The sacral spinal epidural space is an uncommon site for primary malignant lymphomas, presenting with symptoms associated with cauda equina compression. Especially, lumbo-sacral epidural lymphoma has been reported to be very rare. We present a rare case of 29-year-old male with sacral spinal epidural malignant lymphoma. The patient complained of tingling sensation in his buttocks that was radiating to his calf. The neurological examination was normal. Magnetic resonance imaging (MRI) with contrast showed a well-defined extradural mass lesion at the mid L5 to mid S2 level. The lesion was iso- to hypointense on T1 and T2 weighted images and showed homogenous enhancement and a focal enhancement in the L5 vertebral body on post-contrast images. The patient underwent a L5-S2 laminectomy and subtotal excision of the lesion. Intra-operatively, the lesion was extradural and not densely adherent to the dura; the lesion was friable, not firm, fleshy, brownish and hypervascular. The histologic diagnosis was grade 2 non-Hodgkin's follicular lymphoma. Even though the primary spinal epidural non-Hodgkin's lymphoma is a very rare disease, clinicians should take it into consideration in the differential diagnosis of patients with spinal epidural tumor.

What are MRI findings of Spine Benign Metastasizing Leiomyoma? Case report with literature review.

INTRODUCTION: Benign Metastasizing Leiomyoma (BML) is a rare disease that results from metastasis of uterine leiomyoma to distant sites with benign pathologic features. Spine BML is very rare so the information of its features and pathophysiology is seldom known. MATERIALS AND METHODS: We experienced a case of 42-year-old woman who presented with right buttock and leg pain with paresthesia. She had a surgical history of uterine myomectomy. Magnetic resonance imaging (MRI) of the lumbar spine revealed a well-circumscribed mass lesion in the posterior compartment of the L4 vertebral body, with extension into the ventral epidural space and both foramina. The mass showed hypointensity on T1-, T2-weighted images and strong homogeneous enhancement on gadolinium enhanced T1-weighted images. Tumor removal was conducted, and permanent biopsy revealed the mass as leiomyoma. Nine previous spine BML reports, which are known for all, were reviewed along with our case. We collated the clinical information and MRI findings of spine BML to figure out its common denominators. RESULTS: Premenopausal women, previous history of uterine myoma, myomectomy/hysterectomy, and lung BML seemed to be predisposing clinical factors. For the imaging findings, posterior vertebral body invasion with bony destruction, neural foramen invasion, and canal encroachment were shown as common denominators. Especially in MRI findings, low T1 and T2 signal intensities with strong homogeneous enhancement were their common features. CONCLUSION: We gathered the fragmentary information of the spine BML for the first time, especially the MRI findings. Although spine BML is rare, it surely exists. Accordingly, spine surgeons should be suspicious of spine BML given its typical clinical history and MRI findings.

Epidural steroid injection therapy for low back pain: a meta-analysis.

OBJECTIVES: The aim of this study was to systematically assess the long-term (≥ 6 months) benefits of epidural steroid injection therapies for patients with low back pain. METHODS: We identified randomized controlled trials by database searches up to October 2011 and by additional hand searches without language restrictions. Randomized controlled trials on the effects of epidurals for low back pain with follow-up for at least 6 months were included. Outcomes considered were pain relief, functional improvement in 6 to 12 months after epidural steroid injection treatment and the number of patients who underwent subsequent surgery. Meta-analysis was performed using a random-effects model. RESULTS: Twenty-nine articles were selected. The meta-analysis suggested that a significant treatment effect on pain was noted at 6 months of follow-up (weighted mean difference [WMD], -0.41; 95 percent confidence interval [CI], -0.66 to -0.16), but was no longer statistically significant after adjusting for the baseline pain score (WMD, -0.19; 95 percent CI, -0.61 to 0.24). Epidural steroid injection did not improve back-specific disability more than a placebo or other procedure. Epidural steroid injection did not significantly decrease the number of patients who underwent subsequent surgery compared with a placebo or other treatments (relative risk, 1.02; 95 percent CI, 0.83 to 1.24). CONCLUSIONS: A long-term benefit of epidural steroid injections for low back pain was not suggested at 6 months or longer. Introduction of selection bias in the majority of injection studies seems apparent. Baseline adjustment is essential when we evaluate pain as a main outcome of injection therapy.

Preparation of biomimetic hydrogels with controlled cell adhesive properties and topographical features for the study of muscle cell adhesion and proliferation.

Synthetic substrates with defined chemical and structural characteristics may potentially be prepared to mimic the living ECM to regulate cell adhesion and growth. Hydrogels with cell-adhesive peptides (0.28 ± 0.03 nmol peptide cm(-2) , TTA-R-0.5; and 0.91 ± 0.12 nmol peptide cm(-2) , TTA-R-2.0) and/or micro-scaled topographical patterns (10, 25, and 80 µm grooves) are prepared using enzymatic polymerization. The adherent morphology and proliferation of C2C12 skeletal myoblasts and human aortic smooth muscle cells (hAoSM) on the hydrogels are studied. The newly developed hydrogels may be useful in investigating the roles of cell adhesion and substrate surface properties in the communication of adherent cells with the ECM.

Estimated number of korean adults with back pain and population-based associated factors of back pain : data from the fourth Korea national health and nutrition examination survey.

OBJECTIVE: We estimated the number of Korean adults with back pain and evaluated population-based associated factors of back pain from a representative sample data from the Fourth Korea National Health and Nutrition Examination Survey. METHODS: The number of Korean adults who experienced back pain (experienced patients), those who experienced back pain lasting for three or more months during the past year (chronic patients), and those who were currently suffering from back pain (current patients) were estimated by analyzing the data from the fourth Korea National Health and Nutrition Examination Survey conducted in 2007 using surveyfreq procedure of the SAS statistical package. Population-based odds ratios for being experienced, chronic, and current patient according to demographic (age and gender), socioeconomic (education and occupation), and lifestyle factors (smoking, drinking, and exercise) were estimated using surveylogistic procedure. RESULTS: It was estimated that there were 5,554,256 (proportion, 15.4%; 95% CI, 4,809,466 - 6,299,046) experienced patients, 2,060,829 (5.7%; 1,557,413-2,564,246) chronic patients, and 3,084,188 (8.5%; 2,600,197 - 3,568,179) current patients among 36,107,225 Korean adults aged 20-89 years in 2007. Each of explanatory variables was significantly associated with at least one of the response variables for back pain. CONCLUSION: Based on our study results, further efforts to investigate epidemiology of back pain, to evaluate associated factors, and to improve treatment outcomes are needed.

Isolated petroclival craniopharyngioma with aggressive skull base destruction.

We report a rare case of petroclival craniopharyngioma with no connection to the sellar or suprasellar region. MRI and CT images revealed a homogenously enhancing retroclival solid mass with aggressive skull base destruction, mimicking chordoma or aggressive sarcoma. However, there was no calcification or cystic change found in the mass. Here, we report the clinical features and radiographic investigation of this uncommon craniopharyngioma arising primarily in the petroclival region.